tbuckley/cabot-search huggingface dataset:
Abstract 12442: A Systematic Review And Network Meta-analysis In HfpEF Pharmacologic Treatment
Authors: Stefanos Zafeiropoulos, Ioannis Farmakis, Ioannis Milioglou, Ioannis Doundoulakis, Stavros Stavrakis, Grigorios Giamouzis, Javed Butler, George Giannakoulas
Journal: Circulation (2022)

Introduction: Heart failure with preserved ejection fraction (HFpEF) remains a highly prevalent condition with significant morbidity and mortality but limited treatment options. Sodium glucose cotransporter-2 inhibitors (SGLT2i), angiotensin-receptor neprilysin inhibitors (ARNi) and mineralocorticoid receptor antagonists (MRA) are moderately to weakly guideline supported. Yet, the potential gain with combination therapies has not been elucidated. Hypothesis: This study sought to estimate and compare the aggregate treatment benefit of medical therapies for HFpEF. Methods: We performed a systematic reviewed and network meta-analysis, using MEDLINE, Cochrane, and the Web of Science databases for randomized controlled studies from inception to May 2022. We included patients with heart failure and left ventricular ejection fraction &gt;40%, treated with any of the following therapies: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), beta-blockers (BB), MRA, digoxin, ARNi, SGLT2i, and vericiguat. Our analysis assumed additive benefits of each therapy. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF); secondary outcome was all-cause mortality. Results: We identified 14 studies with a total of 26,556 patients, mean age 71 (±8.8), 49% females and mean ejection fraction of 57% (±8%). Mean follow-up time was 24 months. MRA and SGLT2i, were the individual components that reduced the primary outcome [HR =0.82 (95% CI 0.67-0.99 and 0.78 (95% CI 0.68 - 0.91), respectively], while the combination of ACE-i/ARB, BB, MRA and SGLT2i was the only beneficial [HR 0.53 (95% CI 0.30 - 0.95]. None of the explored combinations or individual components were associated with decreased all-cause mortality. Conclusions: In patients with HFpEF, MRA and SGLT2i alone as well as a combination of ACE-i/ARB, BB, MRA and SGLT2i were associated with decreased risk of CV mortality and HHF.
Abstract 12600: Mitral Annular Disjunction: How Accurate Are We? A Cardiovascular MRI Study Defining Risk
Authors: Nasir Hussain, Geeta Bhagia, Mark Doyle, RONALD B WILLIAMS, Geetha Rayarao, Robert W Biederman
Journal: Circulation (2022)

Background: Mitral Annular Disjunction (MAD) refers to embryologic fibrous separation between mitral annular ring and basal left ventricular myocardium. Since its original description, the role of MAD in arrhythmic mitral valve prolapse (MVP) has been subject of active research. In this study we sought to assess prognostic and imaging characteristics of MVP patients with and without underlying MAD. Methods: Patients with posterior or bi-leaflet MVP were retrospectively identified via a review of all patients referred to our cardiac magnetic resonance (CMR) imaging laboratory from January 2015 to May 2022. MVP patients were further stratified by underlying MAD status. CMR characteristics including late gadolinium enhancement (LGE) distribution, clinical characteristics, and data on mitral valve intervention were determined. Results: A total of 100 MVP patients undergoing CMR imaging (52 MVP patients with posterior MAD) were retrospectively identified with female comprising 55% of the cohort. MVP patients with MAD were more likely to have an abnormal basal inferolateral/ papillary muscles LGE (51% vs 21%, p&lt;0.01). Posterior MAD longitudinal disjunction gap in ‘mm’ was a predictor of ventricular tachycardia (VT) [1.23, p=0.03)]. Similarly, posterior MAD as a binary variable was predictor of VT (11, p&lt;0.01), ventricular arrhythmia (composite of VT, and non-sustained VT) (2.4, p=0.03), and major adverse cardiac events (MACE) (composite of VT, syncope, and mitral valve intervention) (2.5, p=0.03). Using ROC curve analysis, a disjunction gap of &gt; 4 mm was predictive of VT (AUC-0.71, p&lt;0.01), and incorporation of LGE in ROC model further improved AUC to 0.78 confirmed via Akaike information criterion (p&lt;0.05), see Figure. Conclusion: Abnormal LGE involving basal inferolateral myocardium and papillary muscles may provide substrate for arrythmia in MVP patients. Further, for the first time, a MAD threshold of &gt; 4 mm is demonstrated to stratify the VT risk.
Abstract 12121: Integrating Ketone Bodies in Multi-Marker Risk Prediction of Incident Heart Failure in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Parag A Chevli, Senthil Selvaraj, Aziz Hammoud, Margery A Connelly, Christopher Defilippi, Joao A Ac Lima, Sadiya S Khan, David M Herrington, Michael D Shapiro, Muthiah Vaduganathan
Journal: Circulation (2022)

Introduction: The Universal Definition of Heart Failure (HF) has incorporated N-terminal proB-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin (hs-cTnT) as markers to identify “stage B” HF (asymptomatic left ventricular dysfunction). Plasma ketone bodies (KB) have demonstrated an association with disease severity in HF patients. A multi-biomarker risk score may improve risk stratification of incident HF in the community. Methods: Participants free of CVD from the Multiethnic Study of Atherosclerosis (MESA) at the baseline visit were included. A multi-biomarker score was developed incorporating NT-proBNP ≥ 125 pg/mL, hs-cTnT ≥ 14 ng/L, and total KB ≥ 75 th percentile (316 μmol/L), with 1 point allocated for each abnormal marker. A multivariable Cox model was used to assess the association between multi-biomarker risk score categories and the risk of incident HF. The 5- year Kaplan Meier estimates for incident HF was determined for each biomarker score. Results: Among 6748 participants there were 383 incident HF events over a median follow-up of 15.7 yrs. Total KB displayed a poor correlation with other biomarkers (r&lt;0.06 for all). The addition of KB to the current standard of care to identify pre-HF (either elevation in NT-proBNP and/or hs-cTnT) improved risk prediction (C-statistic 0.70 vs. 0.73). The 3-biomarker score demonstrated good discrimination for predicting 5-year HF risk [C-statistic 0.74 (95%CI 0.70-0.78)]. A graded association was observed between biomarker score groups and the risk of HF independent of established clinical factors ( Figure ). 8% of participants with biomarker score ≥2 developed HF within 5 yrs, while those with biomarker scores≤1 faced very low risk (≤2% over 5 yrs). Conclusions: The addition of plasma KB to a clinical risk score using routinely collected biomarkers of cardiac injury and stress may further personalize risk estimation and reduce misclassification of those at risk of incident HF.
Abstract 12657: Clinical, Laboratory, and Coronary Plaque Predictors of Atherosclerotic Non-Response to Statin Therapy
Authors: Sophie E van Rosendael, Inge J van den Hoogen, Fay Y Lin, Daniele Andreini, Mouaz H Al-Mallah, Matthew Budoff, Prof. Dr. Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Edoardo Conte, Hugo Marques, Pedro Goncalves, Ilan Gottlieb, Martin Hadamitzky, Jonathon Leipsic, Erica Maffei, Gianluca Pontone, Gilbert L Raff, Sanghoon Shin, Yong-Jin Kim, Byoung Kwon, Eun-Ju Chun, Ji Min Sung, Sang-Eun Lee, Renu Virmani, Habib Samady, Peter H Stone, James K Min, Jagat Narula, Daniel Berman, Jeroen J Bax, Leslee J Shaw, Alexander R Van Rosendael, Hyuk-Jae Chang
Journal: Circulation (2022)

Introduction: Statins reduce major cardiovascular events, but residual risk remains. The study examined determinants of atherosclerotic statin non-response in patients using statins. Hypothesis: We hypothesized that a comprehensive evaluation of atherosclerosis identifies patients that progress atherosclerosis despite the use of statin therapy. Methods: The multi-center PARADIGM registry included patients who underwent serial CCTA ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up CCTA were included. Atherosclerotic statin non-response was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. A secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. Results: We included 649 patients (62.0±9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin non-response. Age, diabetes, hypertension, and all atherosclerotic plaque features (high risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin non response, while only diabetes, the number of high risk plaque features, noncalcified and calcified PAV were independently associated with atherosclerotic statin non-response (OR:1.41 (0.95-2.11), OR:1.15 (1.09-1.21), OR:1.06 (1.02-1.10), OR:1.07 (1.03-1.12), respectively). For the secondary endpoint (N=125, 19.2%), only non-calcified PAV and number of HRP features were the independent determinants (OR:1.08 (1.03-1.13) and OR:1.21 (1.06-1.21), respectively). Conclusions: In patients treated with statins, baseline plaque characterization by plaque burden and high risk plaque is associated with atherosclerotic statin non-response defined as important progression of coronary atherosclerosis. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.
Abstract 12332: Comparative Cost-Effectiveness of Sacubitril-Valsartan, Dapagliflozin, and Empagliflozin in Heart Failure With Reduced Ejection Fraction
Authors: Neil U Parikh, Neal Dixit, Boback Ziaeian, Gregg C Fonarow
Journal: Circulation (2022)

Introduction: The 2022 American College of Cardiology/American Heart Association (ACC/AHA) guidelines established angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors as Class I therapies in heart failure with reduced ejection fraction (HFrEF). Previous analyses have demonstrated the cost-effectiveness of these drugs, but use of different methodologies limit comparison. The objective of this study was to use a singular model to compare the cost-effectiveness of these agents in HFrEF. Methods: A 2-state Markov model was developed to compare the incremental cost-effectiveness ratios of sacubitril-valsartan, dapagliflozin, and empagliflozin. The enalapril arm of the PARADIGM-HF trial served as the control. Data from the PARADIGM-HF, DAPA-HF, and EMPEROR-Reduced trials were used to simulate treatment with sacubitril-valsartan, dapagliflozin, and empagliflozin, respectively. The model used a lifetime time horizon from a United States healthcare perspective. All costs and quality-adjusted life years were discounted 3% annually. The primary outcome was the incremental cost-effectiveness ratio of each treatment compared to control. Results: The incremental cost-effectiveness ratios of sacubitril-valsartan, dapagliflozin, empagliflozin, were $74,111, $72,048, and $118,253, respectively. Figure 1 shows the incremental cost-effectiveness ratios and incremental quality-adjusted life years in the present analysis compared to previously published analyses. Conclusions: In a singular model of patients with HFrEF, sacubitril-valsartan, dapagliflozin, and empagliflozin all met the threshold for intermediate value ($50,000-$150,000 per quality-adjusted life year gained) set by the ACC/AHA.
Abstract 12138: Outcomes of Pediatric Cardiac Transplantation With a Positive Retrospective Crossmatch
Authors: Irene D Lytrivi, Ryan Cantor, paul esteso, Erik L Frandsen, Meredith K Gibbons, James K Kirklin, Devin Koehl, Jacqueline M Lamour, Adam Putchoegl, Svetlana B Shugh, Ryan J Williams, Frank B Pearce
Journal: Circulation (2022)

Introduction: A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. Hypothesis: Children with a + XM have similar long-term survival but higher rate of complications, such as rejection, coronary vasculopathy (CAV), and infection, compared to patients with a negative XM. Methods: The Pediatric Heart Transplant Society Registry database was queried from 2010-2021 for all patients &lt;18 years of age with a known XM. Baseline demographics were compared between + XM and negative XM groups using appropriate parametric and non-parametric group comparisons. Multiphase survival analysis curves were constructed for each outcome to describe both short- and long-term hazard. Similar correlations were performed for different types of + XM (cytotoxic vs Flow). Results: Of 4599 transplants during the study period, XM results were available for 3914, with + XM in 373 (9.5%). There were 70 cases with CDC + XM (39 B-cell, 31 T-cell) and an additional 149 (90 B-cell, 59 T-cell) with flow + XM where CDC XM was either negative, unknown, or not performed. 5-year survival was significantly different in the 2 groups (HR=1.3, p=0.04). Patients with a +XM had shorter time to first rejection (p=.0001) and detection of CAV (p=0.01), while the risk of infection was similar (p=0.11) [Figure]. When comparing CDC+ to Flow+/CDC- patients, there was no difference in 5-year survival or time to first rejection, however CDC+ patients had shorter time to CAV detection (p= 0.01). Conclusions: Pediatric patients transplanted across a + XM experience earlier rejection, earlier development of CAV, and increased graft loss compared to patients with a negative crossmatch. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.
Abstract 12004: Mitochondrial Fission Mediator MiD49 Regulates Proliferation via MYO1C in Pulmonary Arterial Hypertension
Authors: Kuang-Huieh Chen, Asish Das Gupta, Jeffrey Mewburn, Patricia Lima, Stephen L Archer
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction that is partially due to hyperproliferation of apoptosis-resistant pulmonary arterial smooth muscle cells (PASMC). This “pseudoneoplastic phenotype” of PAH PASMC is due, in part, to excessive mitochondrial fission caused by activation of dynamin related protein-1 (Drp-1) and its binding partner MiD49. The mechanism by which MiD49 regulates the proliferation of PASMC is not completely understood. Here we investigate the possibility that MiD49 promotes cellular proliferation by regulating a non-filamentaous class-1 myosin protein, MYO1C. Hypothesis: MiD49 regulates cell proliferation via a MYO1C-dependent mechanism, which is pathologically upregulated in PAH. Methods: MiD49 and MYO1C expression was compared between normal (n=4) vs PAH (n=5) human PASMC using western blot analysis. The colocalization was visualized using super-resolution confocal microscopy. The effects of manipulating MYO1C on cell proliferation and apoptosis were assessed by flowcytometry. Results: MiD49 and MYO1C are upregulated and colocalized in PAH PASMC. The expression of MYO1C positively correlated with MiD49 in PAH. Silencing MiD49 downregulated MYO1C expression whilst augmenting MiD49 upregulated MYO1C. Silencing MYO1C, however, does not affect MiD49 expression, proving that MYO1C is downstream of MiD49. The downregulation of MYO1C by MiD49 silencing is rescued by a proteasomal blockade, MG132. Downregulating MYO1C using siRNA inhibited proliferation, prevented ERK1/2 activation, and induced apoptosis in PAH PASMC. Conclusion: Increased proliferation and apoptosis resistance of PAH PASMC are in part due to the dysregulation of MiD49-MYO1C pathway. Targeting this pathway may have therapeutic implications against PAH.
Abstract 11401: Silent Brain Infarct on MRI Predicts Clinical Stroke/ Transient Ischemic Attack in Mitral Stenosis
Authors: Nitish Naik, ambuj roy, NITIN RAI, Kapil Kumar, Meenakshi Sharma, sanjeev kumar, Priya Jagia, Lakshmy Ramakrishnan, Rakesh Yadav, Gautam Sharma, Sandeep Singh
Journal: Circulation (2022)

Introduction: Mitral stenosis (MS) is associated with a high risk of cardio-embolic events. However, current recommendations for initiating anti-coagulant therapy in patients with MS is limited to patients with atrial fibrillation (AF),atrial thrombi or those with a prior stroke. In patients with moderate to severe MS who are in sinus rhythm there are no firm recommendations for anti-coagulation despite a known higher risk of thromboembolic events. Moreover there is limited data on the prevalence of silent brain infarcts (SBI) in patients with MS. This study evaluated prevalence and predictors of silent and clinical stroke in MS. Methods: A total of 211 patients with moderate to severe MS (mitral valve area ≤ 1.5 cm2) were recruited in the study and were followed up over a7 year period. Patients with existing left atrial clot(s) or prior valvular intervention were excluded from the study. All patients underwent clinical examination, ECG, echocardiogram, and brain MRI on a 1.5T machine. A 24-hour Holter was performed on patients in sinus rhythm. Results: Among 211 patients, 87(41.2%) were male and 140 (66.3%)were in sinus rhythm. Moderate to severe mitral regurgitation and/or aortic regurgitation was present in 31 (14.7%) and 30 (14.2%)patients respectively. SBI was seen in 44 (20.9 %) patients [26 (18.6%)in sinus rhythm and 18(25.4%) in AF]. Female gender (OR 2.3 95% CI 1.01-5.1, p = 0.043), poorer NYHA functional class (Class II OR 16, 95%CI 4.1-62.8, p=0.001; Class III OR 4.1 95%CI 1.2-13.8, p = 0.024),AF (OR 3.8 95%CI 1.6-8.9 p = 0.002) and aortic regurgitation (OR 3.7 95%CI 1.3-10.4 p = 0.011)were associated with increased risk of SBI. Seventeen patients (8%) were lost to follow up. Among 194patients who completed follow up, clinical stroke/TIA occurred in 15 (7.7%) patients. SBI on MRI was associated with a higher risk of clinical stroke/TIA on follow up on multivariate analysis (OR 3.7 95%CI1.26-10.9, p=0.018). Conclusions: Silent brain infarction is present in a significant minority of patients with MS and is predictive of clinical stroke/TIA on follow up.
Abstract 11970: True Prediction Model f Clinical Outcome in Tetralogy of Fallot Using Contraction Fraction From the <i>Single Center Cardiac Magnetic Resonance Outcomes Registry in Tetralogy of Fallot</i>
Authors: Mark A Fogel, Elizabeth Donnelly, Abdullah Mahmood, Keerthi Reddy, Jen Faerber, Xuemei Zhang, Elizabeth Goldmuntz, Matthew A Harris, David Biko, Sara Partington, Stephen Paridon, Michael Mcbride, Victor Ferrari, Kevin Whitehead, Laura M Mercer-Rosa
Journal: Circulation (2022)

Introduction: There are no large scale true prediction models (as opposed to association) to determine predictors of clinical outcomes in repaired tetralogy of Fallot (rTOF) which is the purpose of this study. In addition, right ventricular (RV) contraction fraction (CF), a novel parameter indexing stroke volume (SV) by mass reflecting the amount of blood volume displaced for a given mass has not been studied. Methods: We retrospectively reviewed data of all rTOF pts undergoing cardiac magnetic resonance (CMR) from 2005-2020. Composite outcome 1 (CO1) included death, transplant, ventricular tachycardia and pacemaker placement &amp; composite outcome 2 (CO2) added cardiovascular hospitalizations (CVH) to CO1. For CF, SV was indexed to BSA 1.4 &amp; RV mass was indexed to height 2.7 . An elastic net was utilized to determine variables of significance to enter a Best Subsets logistic regression model. Data was split into training testing sets. Results: 761 rTOF pts were studied with a followup period of 5.1 + 4.2 years. 54 events occurred in total (table). Of all CMR variables considered for CO1, RV CF was the most significant predictor (AUC 0.65) yielding an odds ratio of 0.54 (95% CI 0.34-0.85), P=0.0063. Adding CVH for CO2, both RV CF and left ventricular (LV) mass were significant predictors (AUC 0.74) yielding adjusted odd ratios of 0.60 (95% CI 1.02-1.05), P=0.0063 &amp; 1.03 (95% CI 0.41-0.86), P&lt;0.0001 respectively. RV CF between those who met and didn’t meet CO1 and CO2 endpoints were significantly different (2.0 + 0.76 vs 2.48 + 1.1 cc*cm 2.7 /g*m 1.4 , P=0.006). This was similar to LV mass for CO2 (54.37 + 17.7 vs 69.56 + 26.9 g/m 2 , P=0.015). Conclusion: With this largest study of a true prediction model in rTOF, RV CF is an important novel predictor and should be incorporated in followup of rTOF patients. Adding CVH to CO1 adds LV mass as another predictor. A measure that incorporates all important RV remodeling parameters such as CF should be followed longitudinally to identify patients at risk.
Abstract 11954: Metabolomic Profiles Differentiate Arterial and Venous Polygenic Risk
Authors: Thomas C Gilliland, Jiwoo Lee, Yunfeng Ruan, Buu Truong, Sara Haidermota, Kim Lannery, Megan Wong, Satoshi Koyama, Pradeep Natarajan
Journal: Circulation (2022)

Introduction : Genome-wide association studies reveal genetic correlations between venous and arterial cardiovascular phenotypes, such as venous thromboembolism (VTE), coronary artery disease (CAD), and peripheral arterial disease (PAD). The extent to which these diseases share metabolomic signatures has not been established. Methods : Polygenic risk scores (PRS) for CAD, PAD, and VTE were constructed using PRS-CS with external summary statistics and tested on ~120,000 UK Biobank participants with metabolomic profiling. Linear regression adjusted for age, sex, genotyping array, the first five principal components of ancestry, and statin prescription estimated the effect of polygenic disease risk on 249 metabolites among participants free of prevalent cardiovascular disease. For all metabolomic associations common to at least two diseases, bidirectional two-sample Mendelian randomization tested the causal relationship between metabolite and phenotype. Results : We found 206, 201, and 116 metabolites were associated with genetic risk for CAD, PAD, and VTE, respectively, at an adjusted p-value of 0.001 ( Figure ). Metabolomic profiles were similar between CAD and PAD (R = 0.75, P = 1.25E-46) and CAD and VTE (R = 0.76, P = 8.27E-49), but not between VTE and PAD (R = 0.24, P = 1.21E-4). Mendelian randomization revealed 28 metabolites that increased risk for both CAD and PAD and 2 metabolites that increased risk for CAD but decreased risk for VTE. There were no metabolites with shared causal relationship between PAD and VTE. Conclusions : Polygenic risks for arterial and venous disease are associated with unique metabolomic profiles. Mendelian randomization reveals overlap in causal metabolites between CAD and PAD but little overlap between VTE and either CAD or PAD despite moderate genetic correlation.